The research proposed in this application deals with two aspects of the mechanisms involved in the induction of cleft palate: (a) histocompatibility-linked genes, and (b) glucocorticoid-binding proteins. With regard to the first, it is well established that genes linked to H-2 are involved in determining the susceptibility of mice to cortisone-induced cleft palate. We have obtained evidence that one, and possibly two, of these genes are in the I region and act by complementation. We now wish to study whether this complementation can occur in both the cis and trans configurations. In addition to H-2-linked genes, we have shown that genes linked to H-3 also influence this trait. We propose to study these genes as extensively as possible, and to determine what similarities or differences may exist between these two types of genes. We have also obtained evidence for MHC-linked genes in the rat which influence susceptibility to dexamethasone-induced cleft palate, and we propose to characterize these genes as fully as possible. The second aspect of this application deals with the possibility that genetic differences in glucocorticoid receptors are involved in genetically different susceptibilities to glucocorticoid-induced cleft palate. In collaboration with Drs. Goldman and Litwack, we propose to: (i) determine whether the amount of glucocorticoid receptor in palatal cells of various strains of mice and rats is related to the cleft palate susceptibility of those strains, (ii) study the possible role of histocompatibility-linked genes in determining different levels of receptor proteins, (iii) determine whether the amount of receptor in thymus cells corresponds to the amount in palatal cells, and whether the thymic level of receptor is related to histocompatibility genes, and (iv) develop monoclonal antibodies against various rat glucocorticoid-binding proteins, and use these antibodies in genetic studies.